Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.

Autor:	Andreatta K; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Willkom M; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Martin R; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Chang S; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Wei L; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Liu H; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Liu YP; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Graham H; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Quirk E; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., Martin H; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA., White KL; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2019 Dec 01; Vol. 74 (12), pp. 3555-3564.
DOI:	10.1093/jac/dkz347
Abstrakt:	Objectives: Studies 1878 and 1844 demonstrated non-inferior efficacy of switching suppressed HIV-1-infected adults to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus continuing boosted PI-based triple regimens or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Here, detailed analyses of pre-existing resistance in the two BIC/FTC/TAF switch studies and efficacy at week 48 are described. Methods: Pre-existing resistance was assessed from historical genotypes (documented resistance to study drugs was excluded) and by retrospective baseline proviral archive DNA genotyping from whole blood. Outcomes were based on HIV-1 RNA at week 48 with missing values imputed using the last on-treatment observation carried forward method. Results: Cumulative pre-existing resistance data from historical and proviral genotypes were obtained for 95% (543/570) of participants who switched to BIC/FTC/TAF. Altogether, 40% (217/543) had one or more pre-existing primary resistance substitutions in protease, reverse transcriptase and/or integrase. Pre-switch NRTI resistance was detected in 16% (89/543) of BIC/FTC/TAF-treated participants, with M184V or M184I detected by proviral genotyping in 10% (54/543). At week 48, 98% (561/570) of all BIC/FTC/TAF-treated participants versus 98% (213/217) with pre-existing resistance and 96% (52/54) with archived M184V/I had HIV-1 RNA <50 copies/mL. No BIC/FTC/TAF-treated participants developed treatment-emergent resistance to study drugs. Conclusions: Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. These results indicate that BIC/FTC/TAF is an effective treatment option for suppressed patients, including those with evidence of archived NRTI resistance. (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
Databáze:	MEDLINE
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